The effectiveness and efficiency of diabetes screening in Ontario, Canada: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Little is known about the efficiency and effectiveness of the current level of diabetes screening activity in Ontario where there is universal access to health services. Our study aims were to: (i) determine how often Ontarians are screened for diabetes; (ii) estimate screening efficiency based on the number needed to screen (NNS) to diagnosis one diabetes case; (iii) examine the population effectiveness of screening as estimated by the number of undiagnosed diabetes cases.</p> <p>Methods</p> <p>Ontario respondents of the Canadian Community Health Survey who agreed to have their responses linked to health care data (n = 37,400) provided the cohort. The five-year probabilities of glucose testing and diabetes diagnoses were estimated using a Cox Proportional Hazards Model. We defined NNS as the ratio of diabetes tests to number of diabetes diagnoses over the study period. We estimated the number of undiagnosed diabetes by dividing the number not tested at the end of study period by the NNS.</p> <p>Results</p> <p>80% of women and 66% of men had a blood glucose test within 5 years. The efficiency of screening was estimated by a NNS of 14 among men and 22 among women. 127,100 cases of undiagnosed diabetes were estimated, representing 1.4% of the Ontario adult population. Increasing age, hypertension, immigrant and non-white ethnicity, and number of general practitioner visits were associated with an increased likelihood of having a glucose test (LR χ2 p < 0.001). Low income men were less likely to be tested.</p> <p>Conclusions</p> <p>Diabetes screening was high in this population-based cohort of Ontarians. Screening efficiency varied considerably in the population. Undiagnosed diabetes continues to be prevalent and remains concentrated in the highest risk groups for diabetes, especially among men.</p

Increased CD8+ T cell responses to apoptotic T cell-associated antigens in multiple sclerosis.

BACKGROUND: Here, we evaluated the hypothesis that CD8(+) T cell responses to caspase-cleaved antigens derived from effector T cells undergoing apoptosis, may contribute to multiple sclerosis (MS) immunopathology. METHODS: The percentage of autoreactive CD8(+) T effector cells specific for various apoptotic T cell-associated self-epitopes (apoptotic epitopes) were detected in the peripheral blood and cerebrospinal fluid (CSF) by both enzyme-linked immunospot and dextramers of class I molecules complexed with relevant apoptotic epitopes. Moreover, the capacity of dextramer(+) CD8(+) T cells to produce interferon (IFN)-γ and/or interleukin (IL)-17 in response to the relevant apoptotic epitopes was evaluated by the intracellular cytokine staining. Cross-presentation assay of apoptotic T cells by dendritic cells was also evaluated ex vivo. RESULTS: We found that polyfunctional (IFN-γ and/or IL-17 producing) autoreactive CD8(+) T cells specific for apoptotic epitopes were represented in MS patients with frequencies significantly higher than in healthy donors. These autoreactive CD8(+) T cells with a strong potential to produce IFN-γ or IL-17 in response to the relevant apoptotic epitopes were significantly accumulated in the CSF from the same patients. In addition, the frequencies of these autoreactive CD8(+) T cells correlated with the disease disability. Cross-presentation assay revealed that caspase-cleaved cellular proteins are required to activate apoptotic epitope-specific CD8(+) T cells ex vivo. CONCLUSION: Taken together, these data indicate that apoptotic epitope-specific CD8(+) T cells with strong inflammatory potential are recruited at the level of the inflammatory site, where they may be involved in MS immunopathology through the production of high levels of inflammatory cytokines